N-methyl-2-pyrrolidone → 2-Chloro-6-(3-fluorobenzylamino)isonicotinonitrile

HRID 1963882

Reaction equation

HRID 1963882 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[N:9]=1)[C:5]#[N:6].CN1C(=O)CCC1.[F:18][C:19]1[CH:20]=[C:21]([CH2:25][NH2:26])[CH:22]=[CH:23][CH:24]=1>CCOC(C)=O>[Cl:10][C:8]1[CH:7]=[C:4]([CH:3]=[C:2]([NH:26][CH2:25][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([F:18])[CH:20]=2)[N:9]=1)[C:5]#[N:6]

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 668533-FluorobenzylamineHCID 7359062,6-Dichloroisonicotinonitrile

Product 1

HCID 830730972-Chloro-6-(3-fluorobenzylamino)isonicotinonitrileYield 99.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a scintillation vial containing 2,6-dichloroisonicotinonitrile (500 mg, 2.89 mmol) was added NMP (6 ml) and (3-fluorophenyl)methanamine (868 mg, 6.94 mmol). The homogenous reaction mixture was capped and heated to 110° C. in a oil bath for 1 hr. The reaction mixture was diluted with EtOAc and washed with sat NaHCO3, H2O and sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude residue was purified by column chromatography on silica gel (0-20% EtOAc/Hexane) to give 2-chloro-6-(3-fluorobenzylamino)isonicotinonitrile (750 mg, 95%). LCMS (m/z): 262.0 (MH+), retention time=1.03 min.

Workup

  1. customThe homogenous reaction mixture was capped
  2. washwashed
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by column chromatography on silica gel (0-20% EtOAc/Hexane)

Sources & evidence

ORD record
ord-dd0363d8da1544b588d6c72e1f2f28a4
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Linked notes

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